It is known that generally, in a reaction of 2-alkoxymethyleneacylacetate and substituted hydrazine, there are plurality of reaction sites in 2-alkoxymethyleneacylacetate as each reaction substrate, which causes inferior selectivity of the reaction to form 1,3-disubstituted-pyrazole-4-carboxylate and 1,5-disubstituted-pyrazole-4-carboxylate which is regioisomer thereof as a by-product. Accordingly, in order to obtain the desired pyrazole derivative, a purification process such as silica gel column chromatography, which is difficult to be industrially performed, is usually required. In JP-A-2000-128763 (patent document 1), it is described that a mixture of 1,3- and 1,5-disubstituted-pyrazole-4-carboxylates obtained as a mixture are hydrolyzed, followed by crystallization to give the desired 1,3-disubstituted-pyrazole-4-carboxylic acid. However, in order to obtain the desired product of high purity, it is necessary to perform crystallization under strict pH control, which industrially causes necessity of complicated operations.
In JP-A-1-113371 (patent document 2), there is described a production method of 1,3-disubstituted-pyrazole-4-carboxylate by a reaction of 2-ethoxymethyleneacylacetate and substituted hydrazine. However, there is no detailed description for the yield and selectivity of 1-substituted-3-trifluoromethylpyrazole-4-carboxylate in the present invention.
The present inventors have conducted a reaction of ethyl 2-ethoxymethylene-4,4,4-trifluoroacetoacetate and methyl-hydrazine by using the method described in patent document 2. As a result, the isomer ratio of ethyl 1-methyl-3-trifluoromethylpyrazole-4-carboxylate and its regioisomer of ethyl 1-methyl-5-trifluoromethylpyrazole-4-carboxylate is 76:24, and it is therefore difficult to say that the procedure is a method having good selectivity (see the following Comparative Example 3).
Further, in Example 1 of JP-A-6-199803 (patent document 3), there is described a method of producing ethyl 1-methyl-3-trifluoromethylpyrazole-4-carboxylate by reacting ethyl-2-ethoxymethylene-4,4,4-trifluoroacetoacetate with methylhydrazine in ethanol at a specified temperature. However, it is clearly written that the desired product is obtained as a mixture containing 15% of undesired ethyl-1-methyl-5-trifluoromethylpyrazole-4-carboxylate. Furthermore, according to the method described in this patent, raw materials are required to be charged at a low temperature of −40 to −35° C., so that this method is industrially lacking in economic efficiency.
Further, in JP-A-2000-212166 (patent document 4), there is described a production method of 1-substituted-3-trifluoromethylpyrazole-4-carboxylate using 2-ethoxy-methylene-4,4,4-trifluoroacetoacetate and substituted hydrazine. It is described that 1-substituted-3-trifluoromethylpyrazole-4-carboxylate is obtained in a yield of about 85% according to this method (Examples 2 to 4). On the other hand, there is no description for the formation of 1-substituted-5-trifluoromethylpyrazole-4-carboxylate, which is an isomer. However, it is clearly written in the specification that when 2-ethoxymethyleneacylacetate and alkylhydrazine are allowed to react with each other at 10° C., a mixture of the desired 1,3-dialkylpyrazole-4-carboxylate (yield: 80˜85%) and its regioisomer 1,5-dialkylpyrazole-4-carboxylate (yield: 10˜15%) is obtained, which causes the necessity of purification by distillation in order to obtain the desired product. Furthermore, in the method of this patent, usable solvents are limited, and it is indispensable to conduct the reaction in esters as a solvent (for example, ethyl acetate or dimethyl carbonate). In addition, in order to obtain the desired product with high yield, it is necessary to conduct the reaction at a low temperature of 5 to 10° C. in the beginning of the reaction, and thereafter, at a reflux temperature of the solvent used. Accordingly, it is hard to say to be an industrially advantageous production method.
Moreover, in the methods described in JP-A-1-113371 (patent document 2), JP-A-6-199803 (patent document 3) and JP-A-2000-212166 (patent document 4) mentioned above, anhydrous hydrazines are used as the raw materials. However, anhydrous hydrazines are highly explosive as is well known, so that it is highly dangerous to use them in large amounts on an industrial scale. Accordingly, when the desired 1,3-disubstituted-pyrazole-4-carboxylate can be highly selectively produced with high yield by using hydrazine hydrate or aqueous solution of hydrazine having low explosive properties, it can conceivably become an extremely excellent method as an industrial production method. However, in all of the above-mentioned patent documents 2 to 4, the influence of water on the yield and selectivity of the desired 1,3-disubstituted-pyrazole-4-carboxylate at the time when water coexists in the reaction system is not described at all. Further, as a result that this reaction has been actually conducted in the presence of water, it has become clear that selectivity substantially decreases. It has therefore been revealed that the desired 1,3-disubstituted-pyrazole-4-carboxylate is not necessarily obtained in good selectivity only by conducting the reaction in the presence of water (see the following Comparative Examples 1, 5, 6 and 7).
Patent Document 1: JP-A-2000-128763
Patent Document 2: JP-A-1-113371
Patent Document 3: JP-A-6-199803 (DE4231517A1)
Patent Document 4: JP-A-2000-212166